HOST POLYMORPHISMS AND THE INCIDENCE OF MALARIA IN

Abstract. Mutations in -globin, glucose-6-phosphate dehydrogenase, and promoters for tumor necrosis factor- and inducible nitric oxide synthase (iNOS) were examined for associations with the incidence of symptomatic malaria in a cohort of 307 Ugandan children. After adjustment of incidence rates for age, water source, use of preventative measures, and proximity to mosquito breeding sites, glucose-6-phosphate dehydrogenase A − heterozygous females had a significantly higher incidence of malaria (incidence rate ratio [IRR] 1.63, P 0.03) and a trend towards higher parasite densities (37,100 versus 26,200 parasites/L; P 0.18) compared with wild-type children. Male hemizygotes had trends in the same direction. Heterozygotes for sickle hemoglobin had trends toward a lower incidence of malaria and lower parasite density at presentation. Heterozygotes for the iNOS promoter G954C polymorphism, but not other promoter polymorphisms, had a significantly lower incidence of malaria compared with wild-type children (IRR 0.69, P 0.05). Host polymorphisms appear to impact upon the incidence of uncomplicated malaria in Ugandan children